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CD4-Cell Decline Not Predicted by Viral Load

In untreated patients, baseline plasma viral load accounted for only 4% to 6% of CD4-cell loss.

Higher plasma viral load has been linked to increased risk for HIV disease progression in population studies, but the degree to which plasma viral load explains CD4-cell loss for individual patients is unknown. Now, in a multi-institutional study involving two cohorts of treatment-naive, chronically HIV-infected patients (total, 2801 patients), researchers have calculated the proportion of variability in CD4-cell–loss rate predicted by baseline plasma viral load. All participants had at least 6 months of follow-up, and at least one viral load and two CD4-cell–count measurements (with the initial measurements taken at baseline). Results obtained with the first cohort were validated by analysis of data from a second cohort — participants in the Multicenter AIDS Cohort Study.

For each cohort overall, increased baseline viral load was associated with accelerated CD4-cell decline. Despite that association, only a small proportion of CD4-cell–loss variability (4% to 6%) for individual subjects could be predicted by their baseline viral load. Use of multiple viral load measurements over time minimally increased the degree to which viral load predicted subsequent CD4-cell loss. Analyses restricted to subjects with high viral loads or accounting for the variability in an individual’s CD4-cell–count and viral load measurements over time did not substantially affect the results.

Comment: As noted by the authors, these results are at odds with the widely held notion that plasma viral load is the main determinant of the rate of CD4-cell loss for an individual patient. The findings suggest that baseline viral load, although very useful for assessing response to therapy, should play a limited role in determining when to start antiretroviral therapy. Other variables such as key genetic determinants, degree of T-cell activation, status of thymic function, and lymph tissue status can contribute in a complex, multifactorial manner to the immunologic and clinical sequelae of HIV infection. A better understanding of all the key determinants of CD4-cell loss might yield novel approaches to treatment that could positively affect the host-pathogen balance and add to the benefits seen with antiretroviral therapy.

— Keith Henry, MD

Dr. Henry wrote the editorial that accompanied this study.

Published in AIDS Clinical Care October 23, 2006

Citation(s):

Rodríguez B et al. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 2006 Sep 27; 296:1498-506.

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